Environmental health sciences has evolved from studies that link a single exposure with a disease, to a new understanding of complex mechanisms by which agents in the environment interact at the molecular level to induce disease in individuals who are susceptible by virtue of age, genetics, nutrition, underlying disease or concurrent exposures. While methods of characterizing exposure and disease have improved, challenges remain when there are multiple exposures and the pathogenesis involves complex genetic and host factors. This is particularly apparent among rural populations with a multiplicity of chemical and biological exposures. This application is to continue funding of the Iowa Environmental Health Sciences Research Center (EHSRC) which has as its overarching theme, research and outreach on the adverse health effects of environmental contaminants among rural and agricultural populations. The EHSRC is at the forefront of research on environmental health problems such as rural asthma and other environmental lung diseases, bioaerosol-induced inflammation, innate immune responses to inhaled microorganisms, mechanisms of oxidative stress, and pesticide metabolism. The Center's focus on the rural environment provides the opportunity to conduct innovative mechanistic and population-based research and to translate that research to prevention and treatment through public health initiatives and clinical advancements. Junior scientists are trained to characterize biological response mechanisms and elucidate gene-environment interactions underlying environmental disease. The interdisciplinary research is organized around three Research Clusters: Inflammation &Innate Immunity, Oxidative Stress &Metabolism, and Environmental Lung Disease. A new initiative is the formation of an Environmental Genomics Research Cluster. Three Facility Cores provide cutting edge services and equipment: Integrative Health Sciences Facility, Pulmonary Toxicology Facility, and Environmental Modeling &Exposure Assessment Facility. An Administrative Core manages a highly effective Pilot Grant Program, Career Development Program, and Community Outreach &Education Core. Center goals are: 1) To coordinate and nurture innovative interdisciplinary EHS research with a focus on reducing adverse health effects of environmental contaminants, especially among rural populations;2) To promote and enhance multi-disciplinary collaborations among basic scientists and physician researchers;3) To recruit investigators from within and outside EHS by providing support for Research Clusters and dedicated Facility Cores;4) To provide mentoring, research resources, and salary support to stellar junior investigators to develop their research careers in EHS;and 5) To provide outreach and education to translate research findings to improve the health and environment of rural people.